ENZYME REACTORS FOR THE SYNTHESIS OF PEPTIDE INHIBITORS

用于合成肽抑制剂的酶反应器

• 批准号: 3508780
• 负责人: James B. West
• 金额: $ 24.62万
• 依托单位: BEND RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3508780
• 关键词: ACE inhibitors; acidity /alkalinity; active sites; antihypertensive agents; bioreactors; biotechnology; catalyst; chemical kinetics; chemical models; chemical reaction; chemical structure; drug design /synthesis /production; enzyme substrate analog; high performance liquid chromatography; ion exchange chromatography; nuclear magnetic resonance spectroscopy; papain; peptide chemical synthesis; renin; salts; solvents; synthetic peptide; temperature; thermodynamics; water

Demand is high for synthetic peptides that inhibit aspartyl proteases because of the promise they show for the treatment of serious health disorders such as hypertension. However, conventional techniques for the large-scale preparation of synthetic peptides have drawbacks (e.g., racemization of components, hazards associated with reagents, and laborious purification steps). This program is aimed at the development of a novel peptide-synthesis process that overcome these drawbacks. The approach is based on the use of an enzyme-coated carrier that is used to couple dipeptide derivative and statine analogs to form peptide inhibitors. In Phase I, we successfully demonstrated feasibility, using the enzyme-coated-carrier process to synthesize three model renin inhibitors. In Phase II, we propose to characterize the enzyme-coated-carrier process and develop the information necessary to commercialize the process in Phase III. Specifically, we plan to characterize the process for the production of renin inhibitors, investigate the effect of process variables, demonstrate widespread applicability of the process, identify scale-up tissues, and demonstrate the technical and economic feasibility of the process. We expect to commercialize this process in Phase III through collaboration with a major U.S. pharmaceutical company.

对抑制乙酰基蛋白酶的合成肽的需求很高 因为它们对治疗严重的健康问题 如高血压等疾病。 然而，用于制备纳米颗粒的常规技术并不理想。 合成肽的大规模制备具有缺点（例如， 组分的外消旋化，与试剂相关的危险， 纯化步骤）。 该计划旨在开发一种新的肽合成 克服这些缺点的方法。 该方法基于使用 用于偶联二肽衍生物的酶包被载体， 他汀类似物以形成肽抑制剂。 在第一阶段，我们成功地 证明了可行性，使用酶包被载体工艺， 合成了三种模型肾素抑制剂。 在第二阶段，我们建议对酶包被载体工艺进行表征 并开发必要的信息，以便在第三阶段将该工艺商业化。 三. 具体而言，我们计划描述生产过程的特征 研究工艺变量的影响， 证明该工艺的广泛适用性，确定扩大规模 组织，并证明技术和经济可行性的 过程 我们希望在第三阶段将这一过程商业化， 与美国一家大型制药公司合作。